Diencephalo-telencephalic changes of tyrosine hydroxylase in rats and grass frogs after sleep deprivation

Based on sleep deprivation-produced changes of electrographic parameters of the wakefulness-sleep cycle (WSC) in rats and frogs (Rana temporaria), dynamics of activity of tyrosine hydroxylase, the key enzyme of dopamine synthesis, was studied immunohistochemically in substantia nigra and nigrostriatal pathway in rats and in striatum, paraventricular organ, and extrahypothalamic pathways in frogs. Changes in dynamics of tyrosine hydroxylase in rats and in frogs are revealed after the 6-h sleep deprivation and after 2 h of postdeprivation sleep. This allows determining the degree of participation of corticostriatal neuroregulatory and hypothalamo-pituitary neurosecretory systems and their role in regulation of WSC. Possible evolutionary peculiarities of morphofunctional differences in homoiothermal and poikilothermal animals are discussed.     

Effect of apomorphine on the wakefulness--sleep cycle of the common frog Rana temporaria

This work considers effects of introduction into spinal lymphatic sac of dopamine agonist--apomorphine-(APO) at doses of 0.1, 1.0, 2.0 and 4.0 mg/kg body weight on the common frog wakefulness-sleep cycle (WSC). Usually the frog WSC is represented by wakefulness and three types of passive-protective behavior: by immobility states of the type of catalepsy, catatonia, and cataplexy that are characterized by high thresholds of arousal and by different (corresponding to the name) skeletal musculature tones. These immoboloty forms are considered as homologues of mammalian stress-reaction, hibernation, and sleep. Low apomorphine doses produced in WSC a marked decrease of portion of wakefulness and an increase of the immoboloty state of the catalepsy; high doses, on the contrary, initially promoted in CNS an increase of wakefulness and the state of catalepsy by demonstrating thereby its stressogenic action; after this, in WSC these increased the portion of the sleep-like immobility state of the catalepsy type that is considered as a functional homologue of sleep of homoiotherms. In spectra of electrograms of the flog telencephalon the representation of waves of the delta diapason rose. Taking into account that the states of catalepsy and cataplexy in frogs are under control of the anterior hypothalamus, it can be suggested that manifestations of cataplexy (sleep) in frog are due to the low level of dopaminergic activity, whereas manifestations of catalepsy (the homologue of stress reaction) are due to the high dopamine content in the anterioi hypothalamic structures. Comparative analysis of changes in WSC of amphibians and mammals in response to administration of dopamine and its agonists allows thinking that the role of the dopaminergic neurotransmitter system in regulation of the vertebrate WSC is unanimous: the low level of activity of this system facilitates development of sleep (catalepsy), whereas the high level provides reaction of arousal and is actively included in the system providing stress-reaction.     

Effect of apomorphine on the wakefulness-sleep cycle of the common frog <Emphasis Type="Italic">Rana temporaria</Emphasis>

This work considers effects of introduction into spinal lymphatic sac of dopamine agonist-apomorphine (APO)-at doses of 0.1, 1.0, 2.0, and 4.0 mg/kg body weight on the common frog wakefulness-sleep cycle (WSC). Usually the frog WSC is represented by wakefulness and three types of passive-protective behavior: the immobility states of the type of catalepsy, catatonia, and cataplexy that are characterized by high thresholds of arousal and by different (corresponding to the name) skeletal muscle tones. These immobility forms are considered as homologues of mammalian stressreaction, hibernation, and sleep. Low apomorphine doses produced in WSC a marked decrease of portion of wakefulness and an increase of the immobility state of the catalepsy type; high doses, on the contrary, initially promoted in CNS an increase of wakefulness and the state of catalepsy by demonstrating thereby its stressogenic action; after this, in WSC there increased the portion of the sleep-like immobility state of the catalepsy type that is considered a functional homologue of sleep of homoiothermal animals. In spectra of electrograms of the frog telencephalon the representation of waves of the delta diapason rose. Taking into account that the states of catalepsy and cataplexy in frogs are under control of anterior hypothalamus, it can be suggested that manifestations of cataplexy (sleep) in frog are due to the low level of dopaminergic activity, whereas manifestations of catalepsy (the homologue of stress reaction) are due to the high dopamine content in the anterior hypothalamic structures. Comparative analysis of changes in WSC of amphibians and mammals in response to administration of dopamine and its agonists allows thinking that the role of the dopaminergic neurotransmitter system in regulation of the vertebrate WSC certainly consists in that the low level of activity of this system facilitates development of sleep (catalepsy), whereas the high level provides reaction of arousal and is actively included in the system providing stress-reaction.     

Wakefulness-sleep cycle and hypothalamo-pituitary system of young rat pups on the background of photostimulation

Effects of multiple photostimulations (PS) on behavioral reactions of the 30-day old rats were studied in the “open field” test, on the dynamics of the time EEG parameters of the wakefulness-sleep cycle, and on morpho-functional characteristics of the hypothalamo-pituitary neuroendocrine system. It has been revealed that PS promotes the gradual inhibition of the locomotor activity and exploratory behavior (p < 0.05) and an enhancement of autonomic reactions (p < 0.05) as well as an initial increase of intensity of orientation reactions with a subsequent decrease of their number (in connection with adaptation to a light stimulus), A comparative analysis of time parameters of the wakefulness-sleep cycle (WSC) shows a decrease of the part of wakefulness, the slow-wave and rapid-wave sleep phases with a simultaneous increase of the cataleptic stage and the sleep stage transient to the rapid-wave stage, as well as of the number of microactivations appearing on the sleep background at once after the several first PS. By the 4–5th photostimulations the CWS parameters on the whole are restored, except for the cataleptic stage, whose value remains statistically significantly high. The obtained data indicate the initial total CNS excitation and a decrease of the CWS stability. This conclusion is confirmed by the data of analysis of spectral characteristics of electrograms of cortical, hippocampal, hypothalamic brain parts and of caudate nucleus, which revealed only a brief small increase of δ-waves in the slow-wave sleep phase, but a statistically significant long decrease of power of the EEG δ-and ?-oscillations with a simultaneous power increase of α-components in the rapid-wave sleep. The quantitative parameters of changes of the morpho-functional state of neurosecretory cells of the hypothalamus supraoptic and paraventricular nuclei indicate the stress effect of this performed stimulation. The aspects of interaction of the hypothalamic-cortical and thalamo-cortical levels of the CWS integration on the background of chronic stress are discussed.     

Effects of total sleep deprivation in rats with hereditary predisposition to audiogenic convulsions

In rats of the Krushinskii-Molodkina (KM) line with hereditary predisposition to audiogenic convulsions there were studied effects of total sleep deprivation for 3, 6, and 9 h by a light arousal or a slow rotation in a roller on spectral EEG characteristics in the wakefulness-sleep cycle, organization of the cycle, and intensity of convulsive symptoms at the recovery period. The data are presented on dynamics of recovery of the cycle structure for 12 h of postdeprivation period. It has been established that during and after the total sleep deprivations of any duration no paroxysmal discharges appear in EEG of hippocampus, caudate nucleus, medial central thalamic nucleus, somatosensory, visual, and auditory cerebral cortex in any of states of the wakefulness-sleep cycle. These deprivations were also shown to have no effect on the latent period value and parameters of generalized tonic-clonal audiogenic convulsions. At the same time, after 6 and 9 h of the total sleep deprivations in a slowly rotating roller there was revealed in some animals a change of the type of response to the sound stimulus. Such decrease of reaction of rats to audiogenic stimuli seems to be due to alertness of the animals. It is stated that in the KM rats, with the hidden convulsive syndrome, we failed to activate epileptiform manifestations by the used types and ways of the total sleep deprivations.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 1, 2005, pp. 82–88.Original Russian Text Copyright © 2005 by Vataev, Oganesyan.     

The wakefulness-sleep cycle in rats with a genetic predisposition to catalepsy

Neurophysiological studies on wakefulness-sleep cycle have been made in rats selected for hereditary inclination to catalepsy. It was shown that in these animals, the stage of delta-sleep is significantly reduced, whereas the duration of a superficial slow-wave sleep is increased. In a sleeping phase of the cycle, large amount of spindles in the range of alpha- and beta 1-oscillations was observed, especially significant in electrograms of n. caudatum and sensorimotor cortex. This activity is considered as a pathological manifestation of a transient hypnotic phase which includes the increase in immobilization of a cataleptic type.     

Participation of vertebrate forebrain activating systems in organization of the wakefulness--sleep cycle

The article considers mechanisms of diencephalic-telencephlic interactions in regulation of the wakefulness-sleep cycle in various classes of vertebrates. In such interactions a special role is played by the dopaminergic systems that perform neurosecretory function at the level of diencephalon and neurotransmitter function at the level of telencephalon. Concepts of A. I. Karamyan and A. L. Polenov about the stage pattern of development of CNS and neurosecretory systems are presented as well as the interconnection of dopaminergic and glutamatergic neurotransmitter system in the mammalian neostriatum in the wakefulness-sleep cycle is considered. Comparison of dynamics of expression of the dopamine metabotropic receptors and of the glutamate ionotropic receptors in neostriatum showed unidirectional changes of D1 and AMPA on the background of the 6-h sleep deprivation as well as of D2 and NMDA on the background of postdeprivative sleep. The corticofugal direction of glutamate impulsation and its relatively fast actions allow admitting its triggering action on generation of the sleep-inducing processes in the underlying brain parts.     

Participation of vertebrate forebrain activating systems in organization of the wakefulness-sleep cycle

The article considers mechanisms of diencephalic-telencephalic interactions in regulation of the wakefulness-sleep cycle in various classes of vertebrates. In such interactions a special role is played by the dopaminergic systems that perform neurosecretory function at the level of diencephalon and neurotransmitter function at the level of telencephalon. Concepts of A.I. Karamyan and A.L. Polenov about the stage pattern of development of CNS and neurosecretory systems are presented, as well as the interconnection of dopaminergic and glutamatergic neurotransmitter systems in the mammalian neostriatum in the wakefulness-sleep cycle is considered. Comparison of dynamics of expression of the dopamine metabotropic receptors and of the glutamate ionotropic receptors in neostriatum showed unidirectional changes of D₁ and AMPA on the background of the 6-h sleep deprivation as well as of D₂ and NMDA on the background of postdeprivative sleep. The corticofugal direction of glutamate impulsation and its relatively fast actions allow admitting its triggering action on generation of the sleep-inducing processes in the underlying brain parts.     

Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans

The internal circadian clock and sleep-wake homeostasis regulate the timing of human brain function, physiology, and behavior so that wakefulness and its associated functions are optimal during the solar day and that sleep and its related functions are optimal at night. The maintenance of a normal phase relationship between the internal circadian clock, sleep-wake homeostasis, and the light-dark cycle is crucial for optimal neurobehavioral and physiological function. Here, the authors show that the phase relationship between these factors-the phase angle of entrainment (psi)-is strongly determined by the intrinsic period (tau) of the master circadian clock and the strength of the circadian synchronizer. Melatonin was used as a marker of internal biological time, and circadian period was estimated during a forced desynchrony protocol. The authors observed relationships between the phase angle of entrainment and intrinsic period after exposure to scheduled habitual wakefulness-sleep light-dark cycle conditions inside and outside of the laboratory. Individuals with shorter circadian periods initiated sleep and awakened at a later biological time than did individuals with longer circadian periods. The authors also observed that light exposure history influenced the phase angle of entrainment such that phase angle was shorter following exposure to a moderate bright light (approximately 450 lux)-dark/wakefulness-sleep schedule for 5 days than exposure to the equivalent of an indoor daytime light (approximately 150 lux)-dark/wakefulness-sleep schedule for 2 days. These findings demonstrate that neurobiological and environmental factors interact to regulate the phase angle of entrainment in humans. This finding has important implications for understanding physiological organization by the brain's master circadian clock and may have implications for understanding mechanisms underlying circadian sleep disorders.     

The role of histaminergic system of the brain in the regulation of sleep-wakefulness cycle

The structure and the morphological and neurochemical connections of the histaminergic system of the brain, which plays one of the most important roles in maintaining wakefulness, are considered. The biochemistry of histamine metabolism and histamine receptors is briefly described. The special role of the relation between the histamine system and orexin/hypocretin system is noted. Some examples of the effects of experimental manipulations with the histaminergic system on the wakefulness-sleep cycle are given.     

Seasonal allocation of carbohydrates between above‐ and below‐ground organs of Typha domingensis

Seasonal carbohydrates allocation by Typha domingensis was evaluated to identify the potential physiological weaknesses in the growth cycle of this plant in Lake Burullus, Egypt. Monthly plant samples (February–October 2014) were separated into shoots, roots and rhizomes to evaluate the seasonal changes in water‐soluble carbohydrates (WSC), starch and total non‐structural carbohydrates (TNC) for each plant organ. The present study indicated that rhizomes are strong carbohydrates sink during the life cycle of T. domingensis. Starch represented the greatest part of the TNC pool, surpassing the concentration of WSC 1.8–4.3 times. The WSC, starch and TNC concentrations of T. domingensis below‐ground organs (rhizomes and roots) were high at the beginning of the vegetative period (February); they reached their minima in March to support the shoots growth, then were followed by a gradual increase due to the translocation from shoots. The time when T. domingensis is expected to be most susceptible to a management technique is at the point in the seasonal cycle when the stored carbohydrates are at the lowest (in March).     

Disorders in the menstrual cycle and fertility of women with Hodgkin's disease]

Sixty two women with Hodgkin's disease were questioned about disorders in their menstrual cycle and fertility. Menstrual cycle disorders were noted by 38 respondents, i.e. over 60%. Amenorrhoea persisted in 24 of these women. These disorders were significantly more frequent in patient over 30 year of age. There were 52 labours in the group of 38 women with menstrual cycle disorders prior to them, and 21 labours in a group of 24 women without any abnormalities. Hodgkin's disease was diagnosed in 6 patients during pregnancy: 2 of them were treated with irradiations on the upper part of the body while 4 remained untreated. After radiotherapy, there were 2 deliveries in women of the group with menstrual cycle disorders, and 9 deliveries in women without such disturbances. Answers to the supplied questionnaire did not provide any information on the congenital abnormalities in neonates.     

The evolution of sleep circadian cycle and telencephalo-diencephalic interaction in vertebrates

The modem representations of wakefulness-sleep cycle evolution and the data about dynamics of reactivity of activating and inhibition neurotransmitter systems of the forebrain, converging in striatum, in cold- and warm-blooded vertebrates are considered. The data about dynamics of immune reactivity of vasopressin- and oxytocinergic cells of paraventricular and supraoptical hypothalamic nuclei is presented. On the basis of the obtained results, the idea of the leading role of telencephalo-diencephalic interactions in activation of somnogenic processes and their possible mechanisms is advanced.     

Sister chromatid exchange in lymphocytes in myelodysplastic syndrome

Sister chromatid exchange (SCE), percentage of first, second, third mitoses, blastic transformation index and mitotic index in patients with myelodysplastic syndrome (MDS) (3 with refractory anaemia, 2 with refractory anaemia with sideroblasts, 1 with refractory anaemia with excess of blasts, 4 with refractory anaemia with excess of blasts in transformation) and in 15 healthy volunteers were estimated. Three types of lymphocytes cultures were set up: first with phytohemaglutinin (PHA), second with PHA and bromodeoxyuridine (BRdU), third with BRdU. In healthy persons the SCE frequency was negatively correlated to proliferating rate index, but in MDS such correlation was not found. The lymphocytes cell cycle duration based on percentage of mitoses was longer in MDS patients than in controls. The results of our studies show the disturbances of lymphocytes during cell cycle division resulting in higher SCE frequency and lower proliferating rate compared to controls.     

Modern nondrug methods of human sleep regulation

Nondrug approaches for the regulation and induction of human sleep available at present have been analyzed; an attempt at classifying them has been made. The main attention is paid to the methods using modern computer technologies for the recording and analysis of various characteristics of the functioning of the human body, primarily, its electroencephalogram (EEG). Normal human sleep EEG correlates and their changes during different stages of the wakefulness-sleep cycle are reviewed and modern opportunities to use these characteristics for artificial regulation and induction of human sleep are analyzed.     

Genome-Wide Association of Stem Water Soluble Carbohydrates in Bread Wheat

Water soluble carbohydrates (WSC) in stems play an important role in buffering grain yield in wheat against biotic and abiotic stresses; however, knowledge of genes controlling WSC is very limited. We conducted a genome-wide association study (GWAS) using a high-density 90K SNP array to better understand the genetic basis underlying WSC, and to explore marker-based breeding approaches. WSC was evaluated in an association panel comprising 166 Chinese bread wheat cultivars planted in four environments. Fifty two marker-trait associations (MTAs) distributed across 23 loci were identified for phenotypic best linear unbiased estimates (BLUEs), and 11 MTAs were identified in two or more environments. Liner regression showed a clear dependence of WSC BLUE scores on numbers of favorable (increasing WSC content) and unfavorable alleles (decreasing WSC), indicating that genotypes with higher numbers of favorable or lower numbers of unfavorable alleles had higher WSC content. In silico analysis of flanking sequences of trait-associated SNPs revealed eight candidate genes related to WSC content grouped into two categories based on the type of encoding proteins, namely, defense response proteins and proteins triggered by environmental stresses. The identified SNPs and candidate genes related to WSC provide opportunities for breeding higher WSC wheat cultivars.     

Daily distribution of sleep states in the jackdaw, Corvus monedula

Polygraphic and behavioral studies of the jackdaws Corvus monedula have revealed a strong influence of the natural day-night cycle on their daily wakefulness-sleep activity. The jackdaws were behaviorally active during the light part of the photoperiod. The daily distribution of slow wave sleep (SWS) was symmetric and that of paradoxical sleep (PS) was asymmetric. The amount of PS was greater in the second half of the night than in the first. Short and intermediate length episodes occurred almost homogeneously throughout the night. The longest sleep episodes clustered toward the middle part of the night and did not occur in the periods following onset of sleep and before the end of sleep.     

Effects of Favorable Alleles for Water-Soluble Carbohydrates at Grain Filling on Grain Weight under Drought and Heat Stresses in Wheat

Drought, heat and other abiotic stresses during grain filling can result in reductions in grain weight. Conserved water-soluble carbohydrates (WSC) at early grain filling play an important role in partial compensation of reduced carbon supply. A diverse population of 262 historical winter wheat accessions was used in the present study. There were significant correlations between 1000-grain weight (TGW) and four types of WSC, viz. (1) total WSC at the mid-grain filling stage (14 days after flowering) produced by leaves and non-leaf organs; (2) WSC contributed by current leaf assimilation during the mid-grain filling; (3) WSC in non-leaf organs at the mid-grain filling, excluding the current leaf assimilation; and (4) WSC used for respiration and remobilization during the mid-grain filling. Association and favorable allele analyses of 209 genome-wide SSR markers and the four types of WSC were conducted using a mixed linear model. Seven novel favorable WSC alleles exhibited positive individual contributions to TGW, which were verified under 16 environments. Dosage effects of pyramided favorable WSC alleles and significantly linear correlations between the number of favorable WSC alleles and TGW were observed. Our results suggested that pyramiding more favorable WSC alleles was effective for improving both WSC and grain weight in future wheat breeding programs.     

The phenomenon of lowering a seizure readiness level after frequent audiogenic seizures in Krushinskiĭ-Molodkina rats

The spectral analysis of the EEG activity of several brain structures (somatosensory, visual and auditory areas of the cortex, hippocampus, caudate nucleus and central medial thalamic nucleus) in the wakefulness-sleep cycle in Krushinskii--Molodkina strain rats with inherited predisposition to audiogenic seizures using long-lastint reducing of the seizure readiness level revealed in these animals after frequentative audiogenic generalized tonicclonic seizures, was performed. The reducing susceptibility to convulsiogenic sound stimuli in rats correlated with a decrease of the theta-range' waves level and increase of the expression alpha-range waves in the EEG during wakefulness. Probable role of reorganized functions of ascending activating brain systems in origination of the long reduction of susceptibility to the sound after frequentative audiogenic convulsions in rats is discussed.     

Alzheimer's disease pathogenesis: The role of disturbed sleep in attenuated brain plasticity and neurodegenerative processes

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairments. The classical symptoms of the disease include gradual deterioration of memory and language. Epidemiological studies indicate that around 25–40% of AD patients have sleep-wake cycle disturbances. Importantly, a series of studies suggested that the relationship between AD and sleep disturbance may be complex and bidirectional. Indeed, accumulation of the extracellular neuronal protein amyloid-beta (Aβ) leads to altered sleep-wake behavior in both mice and humans. At the same time, disturbances of the normal sleep-wake cycle may facilitate AD pathogenesis. This paper will review the mechanisms underlying this potential interrelated connection including locus coeruleus damage, reductions in orexin neurotransmission, alterations in melatonin levels, and elevated cytokine levels. In addition, we will also highlight how both the development of AD and sleep disturbances lead to changes in intracellular signaling pathways involved in regulating neuronal plasticity and connectivity, particularly extremes in cofilin phosphorylation. Finally, current pharmacological and nonpharmacological therapeutic approaches will be discussed.